ArticlePathogens (Basel, Switzerland)2022
The Conserved Macrodomain Is a Potential Therapeutic Target for Coronaviruses and Alphaviruses.
Article in Pathogens (Basel, Switzerland), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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The trial behind it
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Who cites it
34 citing papers in PubMed.
- Cellular engagement of the SARS-CoV-2 macrodomain by GS-441524 and enhancedRSC chemical biology · 2026Article
- X-ray Crystallography-Guided Design and Synthesis of Cyclopentyl Heteroaryl Carboxylic Acid-Based Inhibitors of the SARS-CoV-2 Nsp3 Macrodomain (Mac1).Journal of medicinal chemistry · 2026Article
- Targeting SARS-CoV-2 Non-Structural Proteins: A Blueprint for Next-Generation Small-Molecule Coronavirus Antivirals.Pharmaceutics · 2026Review
- Structure, function, regulation, evolution, and therapeutic implications of PARP14.Genes & development · 2026Review
- Screening assay to monitor mono-ADP-ribosylhydrolase activity of viral macrodomains in cells.Communications biology · 2026Article
- Discovery of AVI-6451, a Potent and Selective Inhibitor of the SARS-CoV-2 ADP-Ribosylhydrolase Mac1 with Oral Efficacy In Vivo.Journal of medicinal chemistry · 2026Article
- Article
- Discovery of AVI-6451, a Potent and Selective Inhibitor of the SARS-CoV-2 ADP-Ribosylhydrolase Mac1 with Oral Efficacy in vivo.bioRxiv : the preprint server for biology · 2025Article
- Macrodomain ADP-ribose binding but not ADP-ribosylhydrolase activity is critical for chikungunya virus infection ofbioRxiv : the preprint server for biology · 2025Article
- The Mac1 ADP-ribosylhydrolase is a Therapeutic Target for SARS-CoV-2.bioRxiv : the preprint server for biology · 2025Article
- Mutations differentially affecting the coronavirus Mac1 ADP-ribose binding and hydrolysis activities indicate that it promotes multiple stages of the viral replication cycle.Journal of virology · 2025Article
- Article
- Zinc-finger PARP proteins ADP-ribosylate alphaviral proteins and are required for interferon-γ-mediated antiviral immunity.Science advances · 2025Article
- Identifying novel chemical matter against the Chikungunya virus nsP3 macrodomain through crystallographic fragment screening.bioRxiv : the preprint server for biology · 2024Article
- HTRF-based assay for detection of mono-ADP-ribosyl hydrolyzing macrodomains and inhibitor screening.iScience · 2024Article
- PARP14 and PARP9/DTX3L regulate interferon-induced ADP-ribosylation.The EMBO journal · 2024Article
- PARP14 is regulated by the PARP9/DTX3L complex and promotes interferon γ-induced ADP-ribosylation.The EMBO journal · 2024Article
- Discovery of 2-Amide-3-methylester Thiophenes that Target SARS-CoV-2 Mac1 and Repress Coronavirus Replication, Validating Mac1 as an Antiviral Target.Journal of medicinal chemistry · 2024Article
- Targeting SARS-CoV-2 nonstructural protein 3: Function, structure, inhibition, and perspective in drug discovery.Drug discovery today · 2024Review
- Discovery of 2-amide-3-methylester thiophenes that target SARS-CoV-2 Mac1 and repress coronavirus replication, validating Mac1 as an anti-viral target.bioRxiv : the preprint server for biology · 2023Article
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
Emerging and re-emerging viral diseases pose continuous public health threats, and effective control requires a combination of non-pharmacologic interventions, treatment with antivirals, and prevention with vaccines. The COVID-19 pandemic has demonstrated that the world was least prepared to provide effective treatments. This lack of preparedness has been due, in large part, to a lack of investment in developing a diverse portfolio of antiviral agents, particularly those ready to combat viruses of pandemic potential. Here, we focus on a drug target called macrodomain that is critical for the replication and pathogenesis of alphaviruses and coronaviruses. Some mutations in alphavirus and coronaviral macrodomains are not tolerated for virus replication. In addition, the coronavirus macrodomain suppresses host interferon responses. Therefore, macrodomain inhibitors have the potential to block virus replication and restore the host's protective interferon response. Viral macrodomains offer an attractive antiviral target for developing direct acting antivirals because they are highly conserved and have a structurally well-defined (druggable) binding pocket. Given that this target is distinct from the existing RNA polymerase and protease targets, a macrodomain inhibitor may complement current approaches, pre-empt the threat of resistance and offer opportunities to develop combination therapies for combating COVID-19 and future viral threats.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.